RT Journal Article
SR Electronic
T1 Stress-Related Mediators Stimulate Vascular Endothelial Growth Factor Secretion by Two Ovarian Cancer Cell Lines
JF Clinical Cancer Research
JO Clin Cancer Res
FD American Association for Cancer Research
SP 4514
OP 4521
VO 9
IS 12
A1 Lutgendorf, Susan K.
A1 Cole, Steven
A1 Costanzo, Erin
A1 Bradley, Sarah
A1 Coffin, Jeremy
A1 Jabbari, Sarvenaz
A1 Rainwater, Kaitlin
A1 Ritchie, Justine M.
A1 Yang, Maria
A1 Sood, Anil K.
YR 2003
UL http://clincancerres.aacrjournals.org/content/9/12/4514.abstract
AB Purpose: Stress has long been believed to influence carcinogenesis, but little is known about physiological mechanisms that may underlie these effects. We have recently observed lower levels of vascular endothelial growth factor (VEGF) in ovarian cancer patients with greater social support, whereas higher VEGF was found in patients with greater distress. The goal of this study was to examine possible mechanisms underlying these relationships. Experimental Design: The effects of stress-related mediators including norepinephrine (NE), epinephrine, isoproterenol (a nonspecific β-adrenergic agonist), and cortisol on the production of VEGF by the ovarian cell lines SKOV3 and EG were investigated. Results: NE and isoproterenol significantly enhanced VEGF production by SKOV3 cells, and all three of the adrenergic agonists enhanced VEGF production by EG cells. These effects were blocked by the β antagonist propranolol, supporting a role for β-adrenergic receptors in these effects. Reverse transcriptase-PCR studies indicated constitutive expression of β-1 and β-2 adrenergic receptors on both cell lines. Effects of cortisol on VEGF production varied according to the specific cell line and dose, with stimulating effects on SKOV3 at pharmacologic doses (1000 nm) and on EG at physiological stress level doses (10 nm), and inhibitory effects on EG at pharmacologic doses. Although priming with cortisol blunted NE-induced VEGF production from both cell lines at 3 h, significant increases in VEGF were still seen. Priming with cortisol enhanced isoproterenol-induced VEGF production from SKOV3. Conclusion: These findings provide the first experimental evidence of a pathway by which biobehavioral stress mediators could directly contribute to the progression of ovarian tumors.